Oral Azacitidine Equivalent to Subcutaneous Formulation

An oral formulation of azacitidine plus cedazuridine achieved pharmacokinetic equivalence to subcutaneous azacitidine in patients with myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN), including chronic myelomonocytic leukemia (CMML).

Guillermo Garcia-Manero, MD, of the University of Texas MD Anderson Cancer Center, presented the phase I trial data at the Society of Hematologic Oncology 2024 Annual Meeting in Houston, Texas.

As of July 2023, 65 patients had been treated with eight different dose combinations of oral azacitidine (60–136 mg) and cedazuridine (20–100 mg). The overall population was 36.9% female, participants had a median age of 72 years (range, 26–87), and 6% (n=4) had previously received a hypomethylating agent. In addition, 45 patients had MDS, 16 had CMML, and four had other MDS or MPN.

Oral Azacitidine Combination in MDS or MPN

Dr. Garcia-Manero and colleagues reported that the oral azacitidine formulation plus cedazuridine achieved pharmacokinetic equivalence to subcutaneous azacitidine based on total cycle area under the curve. They also reported that the safety profile was similar, with no unique adverse events (AEs) reported. Grade 3 or higher AEs occurred in 75.9% of patients, the most common of which were leukopenia (25%), thrombocytopenia (20%), and anemia (20%). No dose-limiting toxicities were observed.

In closing, the authors noted that a phase Ib dose-expansion study at the recommended dose combination of 144 mg azacitidine with 20 mg cedazuridine was ongoing to validate the pharmacokinetic equivalence.

Reference

Garcia-Manero G, McCloskey J, Scott BL, et al. Development of oral azacitidine with cedazuridine for myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) including chronic myelomonocytic leukemia (CMML) by targeting pharmacokinetic AUC equivalence vs subcutaneous azacitidine. Abstract #MDS-773. Presented at the Society of Hematologic Oncology 2024 Annual Meeting; September 4-7, 2024; Houston, Texas.